Hemilabile ligands
Douglas Baumgardner
Gilbertson Group
iCID Meeting July 15th, 2019
Historical context
“For some time, we have investigated the chemistry of
phosphine-amine and phosphine-ether ligands with the
expectation that these ligands would bind well enough to allow
isolation but would readily dissociate the “hard” ligand
component, thus generating a vacant site for substrate binding.
We call these ligands hemilabile.”
Jeffrey, J. C.; Rauchfuss, T. B. Inorganic Chemistry 1979, 18 (10), 2658–2666.
In biology
Barondeau, D. P.; Kassmann, C. J.; Bruns, C. K.; Tainer, J. A.; Getzoff, E. D. . Biochemistry 2004, 43 (25), 8038–8047.
Nickel Superoxide Dismutase
2 O2- + 2H+ H2O2 + O2
Types of hemilabilityType 1: This type of hemilabile ligand has a weakly bound ligand that is at equilibrium with an open active site.
Braunstein, P.; Naud, F. Angewandte Chemie International Edition 2001, 40 (4), 680–699.
Yang, H.; Alvarez-Gressier, M.; Lugan, N.; Mathieu, R. Organometallics 1997, 16 (7), 1401–1409.
P. Braunstein, M. Knorr, T. Stährfeldt, J. Chem. Soc. Chem. Commun. 1994, 1913.
Pyridine binds more weakly than the ether due to trans effects
of triphenylphospine
Repeated migratory insertion of CO
Types of hemilability
Type 2: Competing hemilabile ligands
Braunstein, P.; Naud, F. Angewandte Chemie International Edition 2001, 40 (4), 680–699.
Gelling, A.; Noble D. R.; Orell, K. G.; Osborne, A. G.; Sik, V.; J. Chem. Soc. Dalton Trans. 1996, 3065.
“Tick tock” “Windshield wiper”
Types of hemilabilityType 3: The weakly bound portion of the hemilabile ligand is displaced by a substrate,
including electrons
Braunstein, P.; Naud, F. Angewandte Chemie International Edition 2001, 40 (4), 680–699.Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. Progress in Inorganic Chemistry; Karlin, K. D., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2007; pp 233–350.
CO displaces oxide
CO inserts into hemilabile ligand
Generic description of electron activated hemilability
Electron mediated dimerization
Carbon anchored hemilabile ligands
Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. Progress in Inorganic Chemistry; Karlin, K. D., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2007; pp 233–350.
Greco, A.; Green, M.; Stone, F. G. A.; J. Chem. Soc., 1971, (A), 3476
Pang, Z.; Burkey, T. J.; Johnston, R. F.; Organometallics. 1997, 16
Elimination of CO
Hemilabile piano stool complexes
Nitrogen anchored hemilabile ligands
Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. Progress in Inorganic Chemistry; Karlin, K. D., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2007; pp 233–350.
Chottard, J. C.; Mulliez, E.; Girault. J. P.; Mansuy, D.; J. Chem. Soc. Chem. Commun., 1974, 780
W. G. Rohly and K. B. Mertes, J. Am. Chem. Soc., 1980, 102
Van Stein, G. C.; Van Koten, G.; Blank, F.; Taylor, L. C.; Vrieze, K.; Spek, A. L.; Duisenberg, A. J. M.; Schreurs, A. M. M.; Kojić-Prodić, B.; Brevard, C.. Inorganica Chimica Acta 1985, 98 (2),
107–120.
Reversible ethylene bindingVery stable, able to cycle up to 15 times
Biological macromolecule Cu(I) site mimicry
Phosphorus anchored hemilabile ligands
Annibale, V. T.; Song, D. RSC Advances 2013, 3 (29), 11432.
Gudat, D.; Daniels, L. M.; Verkade, J. G.; Organometallics, 1990, 1464 (9)
Lindner, E.; Schreiber, R.; Schneller, T.; Wegner, P.; Mayer, H. A.; Göpel, W.; Ziegler, C. Inorg. Chem. 1996, 35 (2), 514–525.
Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. Progress in Inorganic Chemistry; Karlin, K. D., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2007; pp 233–350.
Reversible acetonitrile binding, active in the copolymerization of
CO and ethylene without solvent
Reversible CO binding
CO2 activation
Hemilabile bond energetics
Lindner, R.; van den Bosch, B.; Lutz, M.; Reek, J. N. H.; van der Vlugt, J. I. Organometallics 2011, 30 (3), 499–510. M. Prince, B.; Brent Gunnoe, T.; R. Cundari, T. Dalton Transactions 2014, 43 (20), 7608–7614.
Calculated energies of (formal) intermediates for the reaction of the COE
complexes [M(L)(COE)] (M = Rh, Ir; L = L1−L3) with isopropyl isocyanide.
Oxy-insertion reaction and calculated bond distances
Met
al-e
ther
ox
yg
en b
on
d d
ista
nce
(Å
)
Reaction step
kCal/mol
kCal/mol
Hemilabile bond energetics
Ligand Effects on Activation Parameters in
Homogeneous Rh-Catalyzed Methanol Carbonylation
Bischoff, S.; Weigt, A.; Miessner, H.; Lücke, B. Energy Fuels 1996, 10 (3), 520–523.
Carbonylation of methanol
a-d = methyl through butyl
substituent at “X”
Allosteric like regulation
Miller, A. J. M. Dalton Trans. 2017, 46 (36), 11987–12000.
Switchable allylbenzene isomerization catalyzed by iridium pincer-crown ether species. A 0.5 M allylbenzene solution in CD2Cl2 was charged with 5 mM κ4-(15c5NCOPiPr)Ir(H)(Cl) (2) and monitored by 1H NMR spectroscopy. Green down arrows mark the time when 2 equiv. of NaBArF
4 was added to switch on catalysis. Red up arrows mark the time at which 2 equiv. of PPNCl were added to switch off catalysis
Initial rates of reaction
Suzuki coupling
Weng, Z.; Teo, S.; Hor, T. S. A. Acc. Chem. Res. 2007, 40 (8), 676–684.
Polymerization with hemilabile ligands
Manna, C. M.; Kaur, A.; Yablon, L. M.; Haeffner, F.; Li, B.; Byers, J. A. J. Am. Chem. Soc. 2015, 137 (45), 14232–14235.
Gilbertson group hemilabile ligand (MNIC)
Conclusions and Outcomes
Hemilabile ligands can:
• Increase stability
• Allow access to active sites that would otherwise be obscured
• Lead to different reactivity
• Probe binding pathways of biomolecules
• Allow for isolation of reactive intermediates
• Have more sites that can be poisoned in catalysis
• Be less predictable
Design principles to consider when designing hemilabile ligands:
• Hard/Soft Acid/Base theory
• Trans influence
• Ring strain/angles
• Sterics
• Electronics (donating/withdrawing)
• Entropic effects/floppiness
• Redox states/activity
• Preferred geometry of Metal